title: HAVcR-1 reduces the integrity of human endothelial tight junctions.
abstract: BACKGROUND
  Hepatitis A virus cellular receptor-1 (HAVcR-1) is the cellular receptor for Hepatotropic picornavirus. Although HAVcR-1 is expressed in every human organ, its natural function remains unknown. This study investigated the location, association and functionality of HAVcR-1 in human endothelial cells.
  
  
  METHODS
  HAVcR-1 was either overexpressed or knocked-down by plasmid electroporation in human umbilical vein endothelial (HECV) cells. Changes in tight junction (TJ) behaviour were assessed using transendothelial resistance, and paracellular permeability. Binding partners and the location of HAVcR-1 protein was assessed using Western blotting/immunofluorescence.
  
  
  RESULTS
  HAVcR-1 co-localised with zonula occludens-1 (ZO-1) and ZO-2 proteins, both of which are involved in the formation, maintenance and function of TJ. The overexpression of HAVcR-1 resulted in reduced TJ formation; knockdown cells were resistant to hepatocyte growth factor (HGF)-mediated TJ disruption. HGF was unable to effect reduced resistance in these cells. HAVcR-1 was co-precipitated with the TJ regulatory factor Ras homolog gene family, member C (Rho C).
  
  
  CONCLUSIONS
  HAVcR-1 may have a novel function as part of the regulatory apparatus for TJ in human endothelial cells.
authors.affiliation: Metastasis & Angiogenesis Research Group, Department of Surgery, Cardiff School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. martinta1@cf.ac.uk
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Harrison
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D018274:Electroporation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D000072596:Hepatitis A Virus Cellular Receptor 1; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
chemical_list: C491143:HAVCR1 protein, human; C066855:HGF protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011991:Receptors, Virus; C569042:TJP1 protein, human; C569046:TJP2 protein, human; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D017228:Hepatocyte Growth Factor